General Anaesthetic

General anaesthetics: Those agents which cause reversible loss of sensation and consciousness by depressing CNS. Characteristics of anaesthesia: 1.       Reversible loss of consciousness and sensation 2.       Analgesia 3.       Muscle relaxation 4.       Abolition of reflexes Properties of ideal anaesthetic: Ø  Should have good analgesic property Ø  Cause muscle relaxation Ø  Should be non irritating Ø  Pleasant Ø  Induction and recovery should be quick Ø  non inflammable Ø  Should be easily administrable Ø  Wide safety of margin (BP, heart, liver, kidney should not affected) Of the available anaesthetic no one is ideal so adjuncts are needed: 1.       Opioids: For analgesia 2.       Benzodiazepines:  To relieve anxiety 3.       H2 blockers: To reduce acid secretion (used when risk of aspiration pneumonia due to acid secretion) 4.       Anticholinergics: Antisecretory  (Glycopyrrolate is preferred over atropine because antisecretory property  of glycopyrrolate is greater than atropine and also cause less tachycardia than atropine) 5.       Antiemetics: To reduce postoperative vomiting Premedication goal: Main/Primary goal: 1.       To relieve anxiety and induce amnesia 2.       Reduction of preoperative pain 3.       To facilitate muscle relaxation Secondary goal: 1.       Reduction of dose of inhalational agents 2.       Reduction of side effects like salivation, vomiting. 3.       Reduction of acid secretion Stages of anaesthesia: 1.       Stage of analgesia: Dream like stage, minor operations can be done 2.       Stage of delirium: Patient struggle (jerky breathing, tight jaws),shout and excited in this stage. Induction agents are used to avoid this stage. 3.       Surgical anaesthesia 4.       Paralysis Classification: Inhalational                                                           Intravenous 1.       Gas                                                     1. Fast acting agents Nitrous oxide (N2O)                                              Thiopentone Xenon                                                                   Propofol       2.       Volatile liquid                                         Methohexitone A.      Halogenated  agents                               Etomidate                        Halothane                                                         2. Slow acting agents                     Isoflurane                                                               a. Benzodiazepines:Diazepam,Midazolam, Lorazepam                                                           Enflurane                                                               b. Dissociative anaesthesia:Ketamine            Desflurane                                                             c.  Opioid agents:Fentanyl                Sevoflurane                                                                   Methoxyflurane B.      Non halogenated Ether Cyclopropane
Drug	Induction/recovery	Analgesic	Muscle Relaxant	Hepatotoxicity	Nephrotoxicity	Smell/irritating	Disadvantages	Uses
Nitrous oxide (laughing gas)	Fast	Good analgesic	Poor muscle relaxation	No effect	No Effect	No irritation, Non inflammable	Risk of anaemia on repeated use (megaloblastic anaemia and bone marrow depression) Laryngospasm- due to impurities of NO and NO2 Cause “Diffusion Hypoxia”	It is used in combination with oxygen For induction not used Used for dental procedures
Ether (induction is highly irritable/unpleasant)	Very slow	Good analgesic	Very Good muscle relaxant	No effect	No effect	Pungent smell, irritating	Respiratory irritation Nausea and vomiting Explosion risk	Cause hyperglycemia (containdicated in diabetic patients)
Halothane (Smooth induction of anaesthesia)	Medium	Not Good analgesic	Poor  muscle relaxant	Risk of hepatotoxicity	Less renal toxic than methoxyflurane	Non irritant, pleasant smell	Cardiac output, blood pressure decrease(hypotension) Hyperthermia Hepatotoxicity Hypotension Cardiac arrhythmia Reduce renal and hepatic blood flow Sensitizes myocardium to Adrenaline Chills	Preferred in children and for asthmatic patients Relaxes uterus so contraindicated in pregnant woman Contraindicated in Pheochromocytoma
Enflurane (induction is irritable)	Medium	Not good analgesic	Good muscle relaxant	Less hepatotoxic than halothane	Less renal toxic than halothane		Hyperthermia Convulsions can induce Cardiac output and blood pressure decrease but after sometime recover	Containdicated in Epilepsy Cause raise in intracranial pressure
Isoflurane (isomer of enflurane) Induction is irritable	Medium	Not good analgesic	Good muscle relaxant	Less hepatotoxic than halothane	Very less effect		Blood pressure decrease Not provokes seizure	Relaxes uterus  Used as alternate to Halothane Intracranial pressure is not raise No sensitization of myocardium to adrenaline Cardiac output is not affected so preferred for cardiac surgery Safe for Pheochromocytoma Used for day care surgery
Desflurane (irritable induction)	Fastest		Good muscle relaxant	No effect	Very less effect	Pungent, unpleasnat taste	Special vaporiser is needed Respiratory tract irritation, cough,bronchospasm	For day care surgery
Sevoflurane (Very smooth induction of anaesthesia)	Fast	Poor analgesic	Good muscle relaxant		Less renal toxic than enflurane	Pleasant	Exacerbate malignant hyperthermia	Preferred for induction in children Used for day care surgery
Methoxyflurane (highly potent inhalational agent) Smooth induction	Slowest		Good muscle relaxant	Hepatotoxicity	Highly Renal toxic		Cause polyuric renal failure due to presence of high content of fluoride
Thiopental (ultra short acting Barbiturate)	Fast induction within 20-30 seconds	Poor analgesic (produce hyperalgesia)	Poor muscle relaxant				Laryngospasm Respiratory depression Hypotension Bronchoconstrictor, Decrease intracranial pressure, Acute Porphyria	Also used for control of convulsions in Status Epilepticus
Ketamine	Fast (onset of actionnis 30 60 second and terminate with in 15.20 minutes)	Very Good analgesic (maximum in all anaesthetic agents)					Increase intracranial pressure and intraocular pressure Increases heart rate, BP and cardiac output, No respiratory depression	Induce dissociative anaesthesia (hallucination) Good bronchodilator so used in asthmatic patients Preferred for induction in children
Opiods (Fentany,alfentanil, sufentanill		Very Good analgesic effect						Shortest acting opiod- remifentanil
Propofol	Fast (onset of action within 20 seconds and recovery after 4-8 minute)	Poor analgesic	No muscle relaxant effect				Cause hypotension Respiratory depression Decrease intracranial pressure Adrenocortical suppression after long use  Pain at injection site	Decrease intracranial pressure Have antiemetic property Used for day care surgery Choice of drug in  malignant hyperthermia
Methohexital (ULTRA SHORT ACTING Barbiturate)	Fast (4-7 minute)						Bronchoconstrictor Decrease intracranial pressure	More potent than thiopentone
Etomidate	Fast (4-8 minute)						Cause nausea and vomiting Injection is painful which cause thrombophlebitis Cause vitamin-C deficiency	Choice of drug in cardiac disease
Xenon (noble gas)	Rapid		Good muscle relaxant	No effect	No effe ct	Inert gas, no irritant action	Cause respiratory depression Highly expensive
Benzodiazepines (midazolam- faster and short acting)	SLOW	No analgesic effect	Muscle relaxant effect	No effect	No effect		Less respiratory depression Hepatic and renal functions are not affected	Lorazepam used as preanaesthetic agent

1.       All inhalational agents are good bronchodilators (halothane show more bronchodilation than others so preferred in asthmatic patients over other agents) except nitrous oxide.

2.       Cyclopropane is preferred for haemorrhagic shock

3.       Chloroform cause hepatotoxicity and hyperglycemia so avoid in diabetic and hepatitis persons

4.       Methoxyflurane cause hepatotoxicity as well as renal failure

5.       Sevoflurane is highly nephrotoxic

6.       Sevoflurane, isoflurane, enflurane exacerbate seizures

7.       Halothane cause hepatotoxicity

8.       Desflurane have unpleasant taste

9.       Halothane sensitizes heart so not used in Pheochromocytoma

10.    All of the inhalational agent cause respiratory depression

11.    Colour of nitrous oxide cylinder-Blue

12.    Colour of Oxygen cylinder- black body but top most part   of cylinder is White

13.    Colour of Carbon-Di-Oxide cylinder- Grey

14.    Halothane is stored in amber coloured glass

15.    All inhalational agents cause increase in Intracranial pressure

16.    Xenon- nearby  an ideal agent

17.    In children- sevoflurane is a choice of agent for inhalational and ketamine is choice of agent for i.v.

18.    Ketamine is used for emergency anaesthesia for person who take meal and full stomach because it not depress pharyngeal reflex

19.    Ketamine-preferred in asthma and copd patient

20.    In epilepsy preferred - thiopentone

21.    In Neurosurgery preferred – isoflurane

22.    fluoride is responsible for renal toxicity: nephrotoxic level in descending order

methoxyflurane>halothane>enflurane>sevoflurane>isoflurane

Mechanism Of Action

Sr.No.	DRUG	RECEPTOR	M.O.A
1	KETAMINE	NMDA	INHIBIT GLUTAMATE MEDIATED CATION (CALCIUM) CHANNELS	KETAMINE BIND ON PHENCYCILIDINE SITE ON NMDA RECEPTOR
2	NITROUS OXIDE	NMDA, ACTIVATE 2 PORE DOMAIN CHANNEL	INHIBIT GLUTAMATE MEDIATED CATION (CALCIUM) CHANNELS,  BY ACTIVATING POTASSIUM CHANNELS
3	CYCLOPROPANE	NMDA, ACTIVATE 2 PORE DOMAIN CHANNEL	INHIBIT GLUTAMATE MEDIATED CATION (CALCIUM) CHANNELS, BY ACTIVATING POTASSIUM CHANNELS
4	XENON	NMDA, ACTIVATE 2 PORE DOMAIN CHANNEL	INHIBIT GLUTAMATE MEDIATED CATION (CALCIUM) CHANNELS, BY ACTIVATING POTASSIUM CHANNELS
5	PROPOFOL	POTENTIATE GLYCINE RECEPTOR ACTIVITY, POTENTIATE GABA-A RECEPTOR ACTIVITY	BY OPENING CHLORIDE ION CHANNELS, CAUSE HYPERPOLARISATION	PROPOFOL (ALL ANAESTHETIC)-SEDATIVE EFFECT IS MEDIATED AFTER BINDING TO BETA-2 SITE OF THE GABA-A RECEPTOR	PROPOFOL- RESPONSE TO NOXIOUS STIMULI IS INHIBITED BY BINDING TO BETA-3 SITE OF GABA-A RECEPTOR
6	ETOMIDATE	POTENTIATE GABA-A RECEPTOR ACTIVITY	BY OPENING CHLORIDE ION CHANNELS, CAUSE HYPERPOLARISATION	ETOMIDATE (ALL ANAESTHETIC)-SEDATIVE EFFECT IS MEDIATED AFTER BINDING TO BETA-2 SITE OF THE GABA-A RECEPTOR	ETOMIDAT- RESPONSE TO NOXIOUS STIMULI IS INHIBITED BY BINDING TO BETA-3 SITE OF GABA-A RECEPTOR
7	BARBITURATES	POTENTIATE GLYCINE RECEPTOR ACTIVITY, POTENTIATE GABA-A RECEPTOR	BY OPENING CHLORIDE ION CHANNELS, CAUSE HYPERPOLARISATION
8	HALOGENATED INHALATIONAL COMPOUNDS	POTENTIATE GABA-A RECEPTOR ACTIVITY	BY OPENING CHLORIDE ION CHANNELS, CAUSE HYPERPOLARISATION
9	BENZODIAZEPINES	POTENTIATE GABA-A RECEPTOR ACTIVITY	BY OPENING CHLORIDE ION CHANNELS, CAUSE HYPERPOLARISATION
Overall M.O.A of general anaesthetics: General Anaesthetics facilitate inhibitory channels (GABA, GLYCINE, POTASSIUM channels) and inhibit excitatory channels  (glutamate and nicotinic channels)